Concise synthesis of telmisartan via decarboxylative cross-coupling.
An efficient synthesis of the angiotensin II receptor antagonist telmisartan is presented involving a decarboxylative cross-coupling of isopropyl phthalate (1) with 2-(4-chlorophenyl)-1,3-dioxolane (2c) as the key step (85% yield). The benzimidazole moiety is constructed regioselectively via a reductive amination-condensation sequence, replacing the previously published route via alkylation of the preformed benzimidazole. The product is obtained in an overall yield of 35% in a convergent synthesis with the longest sequence consisting of eight steps.
Goossen
Lukas J
LJ
Institut für Organische Chemie, TU Kaiserslautern, Erwin-Schrödinger-Strasse, Building 54, D-67663 Kaiserslautern, Germany. goossen@chemie.uni-kl.de
Knauber
Thomas
T
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles / Q000138:chemical synthesis*; D001565:Benzoates / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003653:Decarboxylation; D004148:Dioxolanes; D010795:Phthalic Acids; D000077333:Telmisartan
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001565:Benzoates; D003432:Cross-Linking Reagents; D004148:Dioxolanes; D010795:Phthalic Acids; C032279:phthalic acid; C031000:benzimidazole; D000077333:Telmisartan; C010962:formal glycol